Mechanisms of host iron acquisition by Campylobacter spp

Campylobacters are a food-borne intestinal bacteria that can cause disease in humans but can also live commensally in animals, notably chickens. Iron is an essential nutrient for Campylobacter, required for metabolism and colonisation. In hosts iron is tightly bound to proteins like lactoferrin and haem, meaning Campylobacter requires a number of iron acquisition systems to utilise this iron. Understanding the iron uptake systems used by strains belonging to different host niches will contribute to our understanding of differing host-pathogen interactions and help tackle the disease and its presence in our food supply. The project will have three overarching aims:
1. A phylogenetic analysis of the distributions of iron uptake systems present in different C. jejuni/coli strains in the context of sequence type. Any association with source or host species will be investigated. Insight into the level of redundancy between system components will be sought. The existence of new iron metabolism systems will be investigated within the large isolate database using recently developed tools.
2. The investigation of the mechanism of iron acquisition from lactoferrin by GAPDH and CtuA. GAPDH is essential for oxidative phosphorylation but cell surface GAPDH has been found to also aid in the acquisition of iron from lactoferrin alongside CtuA. The interaction between these proteins will be investigated using protein-protein interaction methods, structural biology and targeted mutations, as will their role in the removal and uptake of iron from lactoferrin.
3. Determination of the role of the chuABCDZ iron uptake system in different host niches. This system is required for iron acquisition from haem and is highly conserved across strains but is not required for intestinal colonisation. Cell invasion and survival assays using chu mutants and different cell types will be used to investigate the role of this system in intracellular and extraintestinal environments.